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PubMed2002

Suppressive effect of polysaccharides from the edible and medicinal mushrooms, Lentinus edodes and Agaricus blazei, on the expression of cytochrome P450s in mice.

To investigate the effects of lentinan from Lentinas edodes and polysaccharides from Agaricus blazei (ABPS) on the expression of cytochrome P450s (CYPs), lentinan (10 mg/kg/day) or ABPS (200 mg/kg/day) was administered to female BALB/c mice four times every other day by intraperitoneal injection. Lentinan and ABPS suppressed both the constitutive and 3-methylcholanthrene-induced CYP1A expression and ethoxyresorufin-O-deethylation activity in the liver.

Agaricales↗
PubMed2003

[Activation of antitumor immunity by intratumor injection of biological preparations].

The antitumor effects of biological response modifiers (BRMs) in an experimental mouse model using a double grafted tumor system were analyzed. Some BRMs prevented metastases by utilizing the anti-tumor immunological cascade reactions, which activate macrophages in the body. The following BRMs were analyzed: PSK was a hot water extract of cultured mycelia from Coliolus versicolor and a protein bound beta-glucan. Lentinan was purified from fruit bodies of Lentinus erodes and is a beta-glucan. The agaricus preparation was extracted from fruit bodies of Agaricus blazei and a protein-bound alpha-, beta-glucan. The M2 fraction was extracted from mycelia of Tricholoma matsutake and was a protein bound alpha-glucan. M1 fraction was purified from mycelia of T. matsutake and was an alpha-glucan. PSK cured both primary and metastatic tumors in the double grafted tumor system. Lentinan did not inhibit the growth of either primary or metastatic tumors. Agaricus preparation cured a primary tumor and inhibited the growth of a metastatic tumor. The M2 fraction prepared from Matsutake inhibited the growth of both primary and metastatic tumors. The M1 fraction did not inhibit either primary or metastatic tumors. Immunosuppressive acidic protein (IAP) is produced by activated macrophages. The PSK, Agaricus preparation and M2 fraction of the Matsutake preparation induced IAP but the lentinan and M1 fraction did not.

Adjuvants, Immunologic↗
PubMed2005

[Antitumor effects of intratumoral injection of Basidiomycetes preparations].

The antitumor effects of Basidiomycetes preparations in an experimental mouse model, the "double grafted tumor system" were analyzed. Some BRMs prevented metastases by utilizing the anti-tumor immunological cascade reactions, which activates macrophages in the body. The following Basidiomycetes preparations were analyzed: PSK was a hot water extract of cultured mycelia from Coliolus versicolor and a protein bound beta-glucan. Matsumax was extracted from mycelia of Tricholoma matsutake and was a protein bound (38%) a-glucan. The Agaricus preparation was extracted from fruit bodies of Agaricus blazei and a protein-bound (17%) a-glucan, beta-glucan. Himematsutake preparation was extracted from fruit body of Agaricus blazei (Himematsutake) and a protein bound (5%) glucan. Lentinan was purified from fruit bodies of Lentinus edodes and is a purified beta-glucan. PSK cured both primary and metastatic tumors in the double grafted tumor system. Lentinan inhibited the growth of neither primary nor metastatic tumors. Matsumax and Agaricus preparation cured primary tumor and inhibited the growth of metastatic tumor. Himematsutake preparation inhibited the growth of primary tumor. Immunosuppresive acidic protein (IAP) is produced by activated mactrophates. The PSK, Matsumax, Agaricus preparation and Himematsutake preparation induced IAP but Lentinan did not.

Agaricus↗
PubMed1988

[Modulation of anticancer effects of immunochemotherapeutic agents in various nutritional environments].

It is well known that some kinds of immunological functions, s.c. NK activity, IFN or IL-2 production of spleen cells are decreased in mice with protein calorie malnutrition (PCM) compared with those of well-nourished mice. In this study, nutritional conditions of cancer bearers were demonstrated to have serious influence on the effects of immunochemotherapeutic agents as shown herewith. (1) Intra-tumoral 5-FU concentration was lower in PCM mice or starved mice than in mice fed a normal diet. (2) Transplanted mammary tumor, MM-48, was paradoxically grown in PCM mice after 7 days i.p. injection of OK-432 or Lentinan, but the tumor burden was relatively decreased after the same treatment in N-group mice. (4) The life prolongation effect of rIL-2 and OK-432 against ascitic hepatic carcinoma, MH-134, was recognized in C 3H/He mice. On the other hand, there was no observable effect by sequential i.p. injection of PCM mice sera together with rIL-2 and OK-432. (5) Clinically, a randomized study of advanced or recurrent gastric cancer patients treated with MMC and FT(MF) with or without Lentinan was performed. Excellent end-point results were obtained only in Lentinan-administered patients with normal protein levels, but no such effects were noted in patients with low protein levels (below 5.9 g/dl). These findings suggest that the nutritional environment of the cancer bearing host has an important role in the effect of some kinds of BRMs.

Animal Nutritional Physiological Phenomena↗
PubMed1988

[Anti-cancer effects of BRMs associated with nutrition in cancer patients].

Nutritional deficiencies are believed to be instrumental in producing reduced immune responses in a variety of animal species. Malnutrition may result in an increase or a decrease in immune functions, depending upon its degree, and also the timing and severity of the nutritional protein deprivation. Our experimental data suggest that there is a significant impairment of cytotoxic activity against K-562 and of the ability of spleen cells to produce interferon in protein-deprived mice in comparison with control mice. Paradoxically accelerated tumor growth after administration of OK-432 or Lentinan was also noted in protein-deficient tumor-bearing mice. In addition, a clinical randomized study of advanced or recurrent gastric cancer patients treated with MMC and FT(MF) with or without lentinan was performed. We recognized excellent end-point results only in the lentinan-treated patients with normal protein levels, while no effect of this agent was seen in patients with low serum protein levels (below 5.9/dl). Aggressive postoperative chemotherapy for cases with distant lymph node metastasis was performed under active nutritional support without any depression of metabolic and immunological states, resulting in a good 5-year survival rate (36.9%).

Adjuvants, Immunologic↗
PubMed1985

Complete regression of Lewis lung carcinoma by cyclophosphamide in combination with immunomodulators.

Several types of combination therapy, including OK432, cyclophosphamide (CY), and/or lentinan plus bacterial lipopolysaccharide (LPS), reported to have strong antitumor activity against some tumors, were only slightly effective on Lewis lung carcinoma (LC) in C57BL/6 mice. Combination therapy by intralesional injection of OK432 followed by intraperitoneal administration of CY, lentinan and LPS caused almost complete regression of intradermal solid-type LC. Maximal antitumor activity was observed when lentinan and LPS were administered later than CY. Mice in which LC had regressed due to this combination therapy showed an antitumor delayed hypersensitivity reaction (measured by the footpad test), but they were not resistant to rechallenge with LC. These results provide a new model for combination therapy against weakly immunogenic tumors.

Animals↗
PubMed1977

Mechanism of the anti-tumour effect of glucans and fructosans: a comparison with C. parvum.

The anti-tumour activity induced by glucans (lentinan, yeast cell walls, pseudonigeran, dextran, DEAE-dextran and dextran sulphate) and fructosans (levan and carboxymethyl-levan) was compared with the activity of C. parvum. The following effects on tumour systems in CBA mice were assayed: (a) adjuvant activity on the immune response against tumour-specific transplantation antigens (TSTA) with a methylcholanthrene-induced fibrosarcoma; (b) cytostatic activity of peritoneal macrophages against radiation-induced leukaemia cells; and (c) inhibition of tumour nodule formation in the lungs following i.v. injection of fibrosarcoma cells. All the polysaccharides induced cytostatic macrophages, but the dextrans and levans did so only after i.p. and not i.v. injection. Only lentinan, yeast cell walls and pseudonigeran were active in the lung-nodule inhibition test; and only lentinan and dextran sulphate showed slight adjuvant activity for TSTA. It is concluded that the anti-tumour activity induced by these polysaccharides is predominantly non-specific macrophage-mediated and much weaker than that found with C. parvum.

Animals↗
PubMedDate not supplied

Effects of OK-432 (picibanil) on the estrogen receptors of MCF-7 cells and potentiation of antiproliferative effects of tamoxifen in combination with OK-432.

OK-432 (picibanil), a streptococcal preparation, has a strong biological response modifier (BRM) function and is expected to produce clinical improvement and prolongation of survival in treated cancer patients in Japan. We were interested in whether OK-432 augments estrogen receptor (ER) levels in breast cancer. To investigate the effect of the BRMs on cellular growth and the characteristics of ER and progesterone receptors (PgR) in the human breast cancer cell line MCF-7, we used OK-432, Krestin (PSK), a protein-bound polysaccharide extracted from Coriolus versicolor, and lentinan, a fungal branched (1...3)-beta-D-glycan. OK432 and PSK dose dependently inhibited DNA synthesis of MCF-7 cells, and the 50% inhibitory concentrations of OK-432 and PSK were 1.2 KE (klinische Einheit, clinical unit)/ml and 200 micrograms/ml, respectively. Lentinan showed no direct anticancer effect in vitro. We found that OK-432 induced a 2-fold increase in ER levels in MCF-7 cells at 0.005 KE/ml, but not in PgR. Lentinan and low-dose PSK did not change ER or PgR levels, but high-dose PSK decreased ER and PgR. We also studied the combined effect of OK-432 and antiestrogens, tamoxifen (TAM) and DP-TAT-59. The combined treatment with OK-432 and TAM showed an additive inhibitory effect on MCF-7 cells. These results suggest that OK-432 may augment the therapeutic effect of TAM in breast cancer.

Antineoplastic Agents↗
PubMed1984

Soluble polyglycans enhance recovery from cobalt-60--induced hemopoietic injury.

Six soluble polyglycans (glucan-C, glucan-F, glucan-S, krestin, lentinan, and schizophyllan), two soluble polymannans (mannan-A and mannan-R), and one soluble polyfructan (levan) were assayed for their ability to enhance hemopoietic recovery in C3H/HeN mice when administered either 1 h before or 1 h after a 6.5-Gy dose of cobalt-60 radiation. Hemopoietic recovery was measured by the endogenous spleen colony assay and was compared with recovery in both radiation control mice and irradiated mice treated with glucan-P (a particulate polyglycan previously shown to enhance recovery from radiation-induced hemopoietic injury). Compared with radiation controls, when administered before irradiation, mannan-A, glucan-F, and glucan-S enhanced endogenous colony formation 4.2-5.1-fold (equivalent to glucan-P), and levan and schizophyllan approximately 2.7-fold. Lentinan, krestin, mannan-R, and glucan-C did not enhance hemopoietic recovery above radiation controls under these conditions. When polyglycan administration was delayed until after irradiation, endogenous colony formation was enhanced 3.0-3.9-fold by mannan-A, schizophyllan, glucan-S, krestin, and glucan-F (at least comparable with glucan-P) but not at all by mannan-R, levan, lentinan, or glucan-C.

Animals↗
PubMed2000

Anti-tumor polysaccharides from mushrooms during storage.

The changes in the contents of an anti-tumor polysaccharide from Lentinus edodes (lentinan) and Grifolafrondosa (GGF) during storage were investigated using by an ELISA inhibition assay. When the mushrooms were stored at low temperature, the contents of their anti-tumor polysaccharides show hardly any changes, but their contents decreased markedly at higher temperature (20 degrees C). Moreover, the effect of the extract from Lentinus edodes stored at different temperatures on tumor necrosis factor (TNF)-alpha and nitric oxide (NO) productions from macrophages was investigated to confirm the influence to the stimulation of macrophages. Because lentinan stimulates macrophages to augment their antitumor activity. Their productions showed little difference between Lentinus edodes stored at low temperature and the fresh mushroom, although the cytokine production decreased significantly in Lentinus edodes stored at 20d egrees C. These results suggest that low-temperature storage is more effective in maintaining not only the quality of the mushrooms but also the contents of anti-tumor polysaccharides as health-beneficient foods.

Agaricales↗
PubMed1992

Two-color flow cytometric analysis of splenic lymphocyte subpopulations in patients with gastric cancer.

Lymphocyte subpopulations of the spleen were assayed in 26 patients with gastric cancer and 5 patients with benign disease using two-color flow cytometric analysis. The ratio of Leu 2a+.Leu 15+ cells, or suppressor T cells, in the gastric cancer patients was about 6 per cent, being higher than that in the patients with benign disease (p less than 0.05). There were fewer Leu 7+.Leu 11- cells, or natural killer-NK-cells, in the gastric cancer patients in stage III or IV than in those with stages I or II (p less than 0.05). The ratio of Leu 3a+.Leu 8- cells, or helper T cells, in the stage IV patients accounted for about 15 per cent of the splenic lymphocytes, which was less than that seen in the patients in stages I or II (p less than 0.05). The ratio of Leu 2a+.Leu 15- cells, or cytotoxic T cells, was approximately twice that of suppressor T cells. The pre-operative administration of lentinan plus OK-432 increased the ratio of Leu 4+.HLA-DR+ cells, or activated T cells, and cytotoxic T cells (p less than 0.05 and p less than 0.01, respectively). The above results suggest that lymphocyte subpopulations in the spleen may have more immunosuppressive potential in proportion with the stage of gastric cancer, but that this reduced immune state may be altered when lentinan and OK-432 are given to these patients.

Adult↗
PubMed1976

Nonspecific macrophage activation by systemic adjuvants. Evaluation by lysosomal enzyme and in vitro tumoricidal activities.

Six systemic adjuvants: living bacillus Calmette-Guérin (BCG), hydrosoluble extracts from BCG and from Mycobacterium smegmatis, bacterial lipopolysaccharide, lentinan and levamisole, have been tested for their ability to induce macrophage activation in mice. The first four adjuvants mentioned increase phosphatase activity of peritoneal macrophages and make them nonspecifically cytotoxic for tumor cells in vitro. The intensity of these phenomena vary with route and time of administration. In contrast, lentinan and levamisole depress both these macrophage activities. Living BCG, extracts from BCG and from M. smegmatis, and the lipopolysaccharide increase the cytotoxic potential of normal macrophages in vitro, suggesting that these agents may exert a direct action on macrophages. Levamisole did not activate normal macrophages in vitro. The existence of a correlation between the capacity of adjuvants to stimulate macrophage tumoricidal activity and their efficiency in active cancer immunotherapy is discussed.

Acid Phosphatase↗
PubMed1980

Immunopotentiating effect of fungal glucans as revealed by frequency limitation of postchemotherapy relapse in experimental mouse tuberculosis.

Two kinds of fungal glucan, particulate yeast glucan (PYG) and lentinan, were examined for their immunopotentiating effect illustrated by reduced frequency of post-chemotherapy relapse in experimental mouse tuberculosis. Infected mice were treated by intensive chemotherapy with a three-drug combination [Streptomycin (SM) + isoniazid (INH) + rifampicin (RFP), ethambutol (EB) + INH + RFP, or SM + INH + pyrazinamide (PZA)] for 5 months. After termination of chemotherapy, the mice of each treated group were divided into three subgroups to receive or not to receive glucan for 4 weeks and again for 4 weeks after a month interval. During this 3-month period and the succeeding 5 months, the mice were subjected to occasional sacrifice to examine the growth of latent tubercle bacilli in the lung and spleen by cultivation of tissue homogenates. The results indicated that the regimens with SM + INH + RFP and EB + INH + RFP were highly effective in eliminating persistent tubercle bacilli down to undetectable levels. However, later multiplication of the latent bacilli was observed during the advanced postchemotherapy period. The application of PYG was most effective in prevention of this type of relapse in the spleen, but not so in the lung. Lentinan effect was manifested in the lung, but not in the spleen.

Adjuvants, Immunologic↗
PubMed1990

[A case of early gastric cancer disappeared by endoscopic polypectomy and local injection of anti-cancer agent associated with systemic immunochemotherapy].

A 78-year-old female was diagnosed as having an early gastric cancer of II a (+II c) type with probable sm invasion by gastroscopic examination. Endoscopic polypectomy was carried out due to advanced age, severe ischemic heart disease, and refusal of surgical treatment. Most of the cancerous tissue were removed endoscopically, but biopsy specimens after polypectomy showed some tumor cells leaving at the excisional site. She was treated with local injection of OK-432 endoscopically, PSK orally, Tegafur rectally, and Lentinan intravenously. After about 7 months' treatments, biopsy specimens revealed no residual cancer cells. The total doses administered up to cure for cancer were 70 KE of OK-432, 141 g of PSK, 99 g of Tegafur, and 45 mg of Lentinan. The combination therapy with massive removal of cancer tissue by endoscopy, local injection of anti-cancer agent to residual cancerous lesion and systemic immunochemotherapy will be available and recommendable for poor risk patients with early gastric cancer.

Adenocarcinoma↗
PubMed1987

Low natural killer syndrome: clinical and immunologic features.

Twenty-three patients with low natural killer syndrome (LNKS), 7 males and 16 females, are reported here. These LNKS patients had an age range from 14 to 77 years, with a median of 36.5 years. LNKS is a newly proposed category of immune disorders, being characteristically diagnosed by lowered NK cell activity against K562 target cells as a definite laboratory abnormality, in association with general clinical symptoms of remittent fever and uncomfortable fatigue, persisting without explanation for more than 6 months. Other immune parameters, such as the DNA synthesis of peripheral blood mononuclear cells (PBMCs) in either the presence or absence of mitogens, the T4+/T8+ ratio and the number of Leu-11+ PBMCs, were usually within the normal range. Also, routine laboratory tests did not detect any abnormal findings. The LNKS patients responded well to the administration of an immunopotentiator called 'lentinan', a glucan extracted from the Japanese mushroom Lentinus edodes, despite no responses to conventional fever treatments such as the administration of antipyretics or antibiotics. All LNKS patients observed were universally free of antibodies in their sera to human T-lymphotropic retroviruses I and III, and lymphadenopathy was infrequent, indicating that the LNKS is a syndrome independent of acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. Antibodies to other known viruses tested such as Epstein-Barr or measles virus, or cytomegalovirus were also negative or not significantly elevated in the sera before the initiation of lentinan administration. If a virus is the cause of LNKS, it may be a new, unknown virus or an unknown substrain of known viruses. None of the LNKS patients has died of this syndrome.

Adolescent↗
PubMed1989

[Two-color analysis of peripheral blood lymphocytes in patients with malignant tumours after low dose half (or total) body irradiation--a pilot study].

The mechanism of anti-tumour effect of low dose total body irradiation applied for non-Hodgkin's lymphoma is still unknown. Two-color analyses of peripheral blood lymphocytes from ten patients with non-Hodgkin's lymphoma or advanced cancer who received low dose total body irradiation (TBI) or half body irradiation (HBI), were performed to be a help to reveal the mechanism. The results of these analyses indicated that the proportion of helper T lymphocytes, helper-inducer T lymphocytes and cytotoxic T lymphocytes increased during TBI or HBI. On the other hand, the proportion of suppressor-inducer T lymphocytes and suppressor T lymphocytes seemed to decrease slightly. The extent of bone marrow suppression of twice-a-week TBI or HBI was clinically no problem, but in the case of thrice-a-week TBI, prolonged bone marrow suppression might occur. In the case of half body irradiated five patients who were administered with lentinan for several weeks to several months before TBI or HBI, the pre-HBI value of the proportion of cytotoxic T lymphocyte fraction was found to be high, and the increment of the proportion of helper T lymphocyte was larger than that of non-lentinan treated cases.

Aged↗
PubMed1988

[Evaluation and consideration of BRM-BRM and HDP (host defense potentiators)].

It should first be stressed that the term BRM is wrong and unscientific, since this would include potassium cyanide or cancer chemotherapeutics in the strict sense of the term. Therefore, in this article we discuss the evaluation of Host Defence Potentiators (HDP). IL-2 or TNF should not be included as HDP because their action is local and not selective to cancer cells, similar to the case of cancer chemotherapeutics. IL-2 is not useful without the presence of IL-2-responsive cells in the host. The most important facet of the action of HDP is to increase the response of the host to cytokines or other bioactive substances according to the degree of maturation, differentiation or proliferation of responsive cells in the host defence mechanism. Lentinan appears to represent a unique class of HDP, markedly potentiating host resistance to cancer and bacterial, viral and parasitic infections, and shows prominent antitumor activity in syngeneic and autochthonous hosts, suppressing chemical and viral oncogenesis. The most important target of HDP is complete prevention of recurrence after "curative" surgery fundamentally through growth inhibition and regression of a small number of autochthonous tumor cells scattered in the host. Considering the excellent end-point results for phase III advanced and recurrent gastrointestinal and breast cancer, lentinan seems to be the most hopeful drug against cancer recurrence. The development of various new types of MDP mediating host homeostasis in the immune, endocrine and nervous systems and nutritional states is expected.

Adjuvants, Immunologic↗
PubMed1987

[Antitumor action of interleukin 2 and its biological activities].

Recombinant IL-2 manifests both proliferation and differentiation-inducing activities in such a way as to generate secondary cytotoxic T lymphocytes (CTL) from memory CTL. IL-2 actually shows antitumor effects against syngeneic tumors, while the combination of IL-2 with chemotherapeutic agents clearly demonstrates complete regression of syngeneic tumors. In addition, the antitumor immunotherapeutic drug lentinan, augments the reactivities of pre-effector cells to IL-2, resulting in the efficient induction of antitumor effectors, CTL, NK and LAK. Combination therapy with lentinan, cyclophosphamide and IL-2 may well be documented as a new rational chemo-immunotherapy in place of adoptive LAK therapy and the infusion of large amounts of IL-2 causing frequent detrimental side effects.

Cyclophosphamide↗